Is CNST p.Pro384Arg (c.1151C>G) pathogenic?

CNST p.Pro384Arg (c.1151C>G) is classified Likely benign in CNST (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.0628); Very rare (popmax 0.00288%, nfe).

How common is CNST p.Pro384Arg (c.1151C>G) in the general population?

CNST p.Pro384Arg (c.1151C>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about CNST p.Pro384Arg (c.1151C>G)?

AlphaMissense predicts likely benign (score 0.0628) — an in-silico prediction, not a clinical call.

CNST p.Pro384Arg

c.1151C>G · rs527643302 · VCV3146671

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0628	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 0.17
Regional constraint	o/e 1.00	unconstrained · MANE · 74 kb · p 0.93 · regional, not allelic
Overall
CADD	9.812	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,180,044 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00217% 35/1,614,008 alleles · very rare exomes 29/1,461,860 · genomes 6/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,707
African / African-American	0.00133%	74,914

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CNST
Protein: p.Pro384Arg
Coding: c.1151C>G
MANE Select: NM_152609
dbSNP: rs527643302
Type: single nucleotide variant
Location: chr1:246647352 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.99
Residue 384: the 'disordered' region

Full CNST gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNST p.Ala134Pro Uncertain significance ★ ⚠ same type
CNST p.Ala144Thr Uncertain significance ★ ⚠ same type
CNST p.Ala403Ser Uncertain significance ★ ⚠ same type
CNST p.Ala407Ser Uncertain significance ★ ⚠ same type
CNST p.Ala499Val Uncertain significance ★ ⚠ same type
CNST p.Ala635Val Uncertain significance ★ ⚠ same type
CNST p.Arg115Ile Uncertain significance ★ ⚠ same type
CNST p.Arg115Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cnst-p-pro384arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown